Intestinal transport of 3H-digitoxin in vitro incompatible with simple diffusion

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Abstract
Summary On everted jejunal segments of mice the transfer and tissue uptake of 3H-digitoxin, over a concentration range from 2×10−10–1×10−4M, was investigated from the mucosal (“m”) to the serosal (“s”) side as well as in the opposite direction. 1. The time course of the absorption of 3H-digitoxin and some other compounds investigated (glucose, urea, p-aminohippurate) gave evidence of functional integrity throughout the 75 min-periods of the experiments. 2. When 3H-digitoxin was applied to the mucosal side the permeability coeffcient showed a dose-dependent increase but returned to lower values at higher concentrations. When 3H-digitoxin was administered to the serosal side the permeability coefficient showed a dose-dependent decrease at high concentrations. The ratio of both coefficients “m” → “s”/“s” → “m” increased dose-dependently from 0.4–2.6. 3. The uptake of 3H-digitoxin — applied on the serosal side — into the tissue was independent of dose. However, having administered 3H-digitoxin on the mucosal side the tissue accumulation was 2–5 fold higher and the tissue/medium (T/M) ratio increased within the concentration range from 3.0–9.0. 4. Under DNP (1 mM) the asymmetry and dose dependence of the permeability and tissue uptake of 3H-digitoxin observed in controls were almost abolished. Therefore it is likely that the transfer of 3H-digitoxin in the intestine involves a mechanism more complex than simple diffusion. The existence of more than a two compartment system and/or the contribution of an active transport mechanism is suggested.